Identification of hematomas in mild traumatic brain injury using an index of quantitative brain electrical activity

Rapid identification of traumatic intracranial hematomas following closed head injury represents a significant health care need because of the potentially life-threatening risk they present. This study demonstrates the clinical utility of an index of brain electrical activity used to identify intracranial hematomas in traumatic brain injury (TBI) presenting to the emergency department (ED). Brain electrical activity was recorded from a limited montage located on the forehead of 394 closed head injured patients who were referred for CT scans as part of their standard ED assessment. A total of 116 of these patients were found to be CT positive (CT+), of which 46 patients with traumatic intracranial hematomas (CT+) were identified for study. A total of 278 patients were found to be CT negative (CT−) and were used as controls. CT scans were subjected to quanitative measurements of volume of blood and distance of bleed from recording electrodes by blinded independent experts, implementing a validated method for hematoma measurement. Using an algorithm based on brain electrical activity developed on a large independent cohort of TBI patients and controls (TBI-Index), patients were classified as either positive or negative for structural brain injury. Sensitivity to hematomas was found to be 95.7% (95% CI=85.2, 99.5), specificity was 43.9% (95% CI=38.0, 49.9). There was no significant relationship between the TBI-Index and distance of the bleed from recording sites (F=0.044, p=0.833), or volume of blood measured F=0.179, p=0.674). Results of this study are a validation and extension of previously published retrospective findings in an independent population, and provide evidence that a TBI-Index for structural brain injury is a highly sensitive measure for the detection of potentially life-threatening traumatic intracranial hematomas, and could contribute to the rapid, quantitative evaluation and treatment of such patients

Type Ia Supernova Light Curve Inference: Hierarchical Bayesian Analysis in the Near Infrared

We present a comprehensive statistical analysis of the properties of Type Ia SN light curves in the near infrared using recent data from PAIRITEL and the literature. We construct a hierarchical Bayesian framework, incorporating several uncertainties including photometric error, peculiar velocities, dust extinction and intrinsic variations, for coherent statistical inference. SN Ia light curve inferences are drawn from the global posterior probability of parameters describing both individual supernovae and the population conditioned on the entire SN Ia NIR dataset. The logical structure of the hierarchical model is represented by a directed acyclic graph. Fully Bayesian analysis of the model and data is enabled by an efficient MCMC algorithm exploiting the conditional structure using Gibbs sampling. We apply this framework to the JHK_s SN Ia light curve data. A new light curve model captures the observed J-band light curve shape variations. The intrinsic variances in peak absolute magnitudes are: sigma(M_J) = 0.17 +/- 0.03, sigma(M_H) = 0.11 +/- 0.03, and sigma(M_Ks) = 0.19 +/- 0.04. We describe the first quantitative evidence for correlations between the NIR absolute magnitudes and J-band light curve shapes, and demonstrate their utility for distance estimation. The average residual in the Hubble diagram for the training set SN at cz > 2000 km/s is 0.10 mag. The new application of bootstrap cross-validation to SN Ia light curve inference tests the sensitivity of the model fit to the finite sample and estimates the prediction error at 0.15 mag. These results demonstrate that SN Ia NIR light curves are as effective as optical light curves, and, because they are less vulnerable to dust absorption, they have great potential as precise and accurate cosmological distance indicators.Comment: 24 pages, 15 figures, 4 tables. Accepted for publication in ApJ. Corrected typo, added references, minor edit

Observations and Implications of the Star Formation History of the LMC

We present derivations of star formation histories based on color-magnitude diagrams of three fields in the LMC from HST/WFPC2 observations. A significant component of stars older than 4 Gyr is required to match the observed color-magnitude diagrams. Models with a dispersion-free age-metallicity relation are unable to reproduce the width of the observed main sequence; models with a range of metallicity at a given age provide a much better fit. Such models allow us to construct complete ``population boxes'' for the LMC based entirely on color-magnitude diagrams; remarkably, these qualitatively reproduce the age-metallicity relation observed in LMC clusters. We discuss some of the uncertainties in deriving star formation histories. We find, independently of the models, that the LMC bar field has a larger relative component of older stars than the outer fields. The main implications suggested by this study are: 1) the star formation history of field stars appears to differ from the age distribution of clusters, 2) there is no obvious evidence for bursty star formation, but our ability to measure bursts shorter in duration than $\sim$ 25% of any given age is limited by the statistics of the observed number of stars, 3) there may be some correlation of the star formation rate with the last close passage of the LMC/SMC/Milky Way, but there is no dramatic effect, and 4) the derived star formation history is probably consistent with observed abundances, based on recent chemical evolution models.Comment: Accepted by AJ, 36 pages including 12 figure

Stellar Populations in Three Outer Fields of the LMC

We present HST photometry for three fields in the outer disk of the LMC extending approximately four magnitudes below the faintest main sequence turnoff. We cannot detect any strongly significant differences in the stellar populations of the three fields based on the morphologies of the color-magnitude diagrams, the luminosity functions, and the relative numbers of stars in different evolutionary stages. Our observations therefore suggest similar star formation histories in these regions, although some variations are certainly allowed. The fields are located in two regions of the LMC: one is in the north-east field and two are located in the north-west. Under the assumption of a common star formation history, we combine the three fields with ground-based data at the same location as one of the fields to improve statistics for the brightest stars. We compare this stellar population with those predicted from several simple star formation histories suggested in the literature, using a combination of the R-method of Bertelli et al (1992) and comparisons with the observed luminosity function. The only model which we consider that is not rejected by the observations is one in which the star formation rate is roughly constant for most of the LMC's history and then increases by a factor of three about 2 Gyr ago. Such a model has roughly equal numbers of stars older and younger than 4 Gyr, and thus is not dominated by young stars. This star formation history, combined with a closed box chemical evolution model, is consistent with observations that the metallicity of the LMC has doubled in the past 2 Gyr.Comment: 30 pages, includes 10 postscript figures. Figure 1 avaiable at ftp://charon.nmsu.edu/pub/mgeha/LMC. Accepted for publication in Astronomical Journa

Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial

Background: Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome. Methods: In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134. Findings: Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88–1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90–1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41–0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22–3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31–0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64–0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37–3·91], p=0·771) was similar. Interpretation: In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status

Perturbation evolution in cosmologies with a decaying cosmological constant

Structure formation models with a cosmological constant are successful in explaining large-scale structure data, but are threatened by the magnitude-redshift relation for Type Ia supernovae. This has led to discussion of models where the cosmological `constant' decays with time, which might anyway be better motivated in a particle physics context. The simplest such models are based on scalar fields, and general covariance demands that a time-evolving scalar field also supports spatial perturbations. We consider the effect of such perturbations on the growth of adiabatic energy density perturbations in a cold dark matter component. We study two types of model, one based on an exponential potential for the scalar field and the other on a pseudo-Nambu Goldstone boson. For each potential, we study two different scenarios, one where the scalar field presently behaves as a decaying cosmological constant and one where it behaves as dust. The initial scalar field perturbations are fixed by the adiabatic condition, as expected from the inflationary cosmology, though in fact we show that the choice of initial condition is of little importance. Calculations are carried out in both the zero-shear (conformal newtonian) and uniform-curvature gauges. We find that both potentials allow models which can provide a successful alternative to cosmological constant models.Comment: 14 pages RevTeX file with three figures incorporated (uses RevTeX and epsf). Also available by e-mailing ARL, or by WWW at http://star-www.maps.susx.ac.uk/papers/lsstru_papers.html Revised version corrects an error in Eq10; results unchange

The SAMI Galaxy Survey: Cubism and covariance, putting round pegs into square holes

We present a methodology for the regularization and combination of sparse sampled and irregularly gridded observations from fibre-optic multiobject integral field spectroscopy. The approach minimizes interpolation and retains image resolution on combining subpixel dithered data. We discuss the methodology in the context of the Sydney-AAO multiobject integral field spectrograph (SAMI) Galaxy Survey underway at the Anglo-Australian Telescope. The SAMI instrument uses 13 fibre bundles to perform high-multiplex integral field spectroscopy across a 1° diameter field of view. The SAMI Galaxy Survey is targeting ~3000 galaxies drawn from the full range of galaxy environments. We demonstrate the subcritical sampling of the seeing and incomplete fill factor for the integral field bundles results in only a 10 per cent degradation in the final image resolution recovered. We also implement a new methodology for tracking covariance between elements of the resulting data cubes which retains 90 per cent of the covariance information while incurring only a modest increase in the survey data volume

Efficacy and safety of minimally invasive surgery with thrombolysis in intracerebral haemorrhage evacuation (MISTIE III): a randomised, controlled, open-label, blinded endpoint phase 3 trial

Acute stroke due to supratentorial intracerebral haemorrhage is associated with high morbidity and mortality. Open craniotomy haematoma evacuation has not been found to have any benefit in large randomised trials. We assessed whether minimally invasive catheter evacuation followed by thrombolysis (MISTIE), with the aim of decreasing clot size to 15 mL or less, would improve functional outcome in patients with intracerebral haemorrhage. MISTIE III was an open-label, blinded endpoint, phase 3 trial done at 78 hospitals in the USA, Canada, Europe, Australia, and Asia. We enrolled patients aged 18 years or older with spontaneous, non-traumatic, supratentorial intracerebral haemorrhage of 30 mL or more. We used a computer-generated number sequence with a block size of four or six to centrally randomise patients to image-guided MISTIE treatment (1·0 mg alteplase every 8 h for up to nine doses) or standard medical care. Primary outcome was good functional outcome, defined as the proportion of patients who achieved a modified Rankin Scale (mRS) score of 0-3 at 365 days, adjusted for group differences in prespecified baseline covariates (stability intracerebral haemorrhage size, age, Glasgow Coma Scale, stability intraventricular haemorrhage size, and clot location). Analysis of the primary efficacy outcome was done in the modified intention-to-treat (mITT) population, which included all eligible, randomly assigned patients who were exposed to treatment. All randomly assigned patients were included in the safety analysis. This study is registered with ClinicalTrials.gov, number NCT01827046. Between Dec 30, 2013, and Aug 15, 2017, 506 patients were randomly allocated: 255 (50%) to the MISTIE group and 251 (50%) to standard medical care. 499 patients (n=250 in the MISTIE group; n=249 in the standard medical care group) received treatment and were included in the mITT analysis set. The mITT primary adjusted efficacy analysis estimated that 45% of patients in the MISTIE group and 41% patients in the standard medical care group had achieved an mRS score of 0-3 at 365 days (adjusted risk difference 4% [95% CI -4 to 12]; p=0·33). Sensitivity analyses of 365-day mRS using generalised ordered logistic regression models adjusted for baseline variables showed that the estimated odds ratios comparing MISTIE with standard medical care for mRS scores higher than 5 versus 5 or less, higher than 4 versus 4 or less, higher than 3 versus 3 or less, and higher than 2 versus 2 or less were 0·60 (p=0·03), 0·84 (p=0·42), 0·87 (p=0·49), and 0·82 (p=0·44), respectively. At 7 days, two (1%) of 255 patients in the MISTIE group and ten (4%) of 251 patients in the standard medical care group had died (p=0·02) and at 30 days, 24 (9%) patients in the MISTIE group and 37 (15%) patients in the standard medical care group had died (p=0·07). The number of patients with symptomatic bleeding and brain bacterial infections was similar between the MISTIE and standard medical care groups (six [2%] of 255 patients vs three [1%] of 251 patients; p=0·33 for symptomatic bleeding; two [1%] of 255 patients vs 0 [0%] of 251 patients; p=0·16 for brain bacterial infections). At 30 days, 76 (30%) of 255 patients in the MISTIE group and 84 (33%) of 251 patients in the standard medical care group had one or more serious adverse event, and the difference in number of serious adverse events between the groups was statistically significant (p=0·012). For moderate to large intracerebral haemorrhage, MISTIE did not improve the proportion of patients who achieved a good response 365 days after intracerebral haemorrhage. The procedure was safely adopted by our sample of surgeons. National Institute of Neurological Disorders and Stroke and Genentech. [Abstract copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.